期刊
BIOCHEMICAL JOURNAL
卷 386, 期 -, 页码 543-547出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20041084
关键词
N-1-acetylpolyamine oxidase (PAO); hydrogen peroxide (H2O2); polyamine; reactive oxygen species; spermidine/spermine N-1-acetyltransferase (SSAT); spermine oxidase [SMO(PAOh1)]
资金
- NCI NIH HHS [CA88843, CA98454, CA51085, CA85509, R01 CA098454, P50 CA088843, R01 CA051085, R01 CA085509] Funding Source: Medline
The oxidation of polyamines induced by antitumour polyamine analogues has been associated with tumour response to specific agents. The human spermine oxidase, SMO(PAOh1), is one enzyme that may play a direct role in the cellular response to the antitumour polyamine analogues. In the present study, the induction of SMO(PAOh1) enzyme activity by CPENSpm [N-1-ethyl-N-11(cyclopropyl)methyl-4,8,diazaundecane] is demonstrated to be a result of newly synthesized mRNA and protein. Inhibition of new RNA synthesis by actinomycin D inhibits both the appearance of SMO(PAOh1) mRNA and enzyme activity. Similarly, inhibition of newly synthesized protein with cycloheximide prevents analogue-induced enzyme activity. Half-life determinations indicate that stabilization of SMO(PAOh1) protein does not play a significant role in analogue-induced activity. However, half-life experiments using actinomycin D indicate that CPENSpm treatment not only increases mRNA expression, but also leads to a significant increase in mRNA half-life (17.1 and 8.8 h for CPENSpm-treated cells and control respectively). Using reporter constructs encompassing the SMO(PAOh1) promoter region, a 30-90% increase in transcription is observed after exposure to CPENSpm. The present results are consistent with the hypothesis that analogue-induced expression of SMO(PAOh1) is a result of increased transcription and stabilization of SMO(PAOh1) mRNA, leading to increased protein production and enzyme activity. These data indicate that the major level of control of SMO(PAOh1) expression in response to polyamine analogues exposure is at the level of mRNA.
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